A Cohort Study of Incretin-based Therapy Combined With Insulin in Type 2 Diabetic Patients for 5 Years

• Death [ Time Frame: Duration varied between individual patients and was as the period of time after treatment with incretin-based therapy combined with insulin. ] [ Designated as safety issue: Yes ]
  The cause of death was determined by attending doctor or was assessed by interviewing the family.
  
  

• HbA1c [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
  Duration varied between individual patients and was as the period of time until after treatment with incretin-based therapy combined with insulin.
  
  
• BMI [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
  BMI was calculated from body weight and height for at baseline and every 3 to 6 months throughout the study.
  
  
• Blood pressure [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
  Participants were examined using the same methods reported previously (4). Briefly, BP was measured in the clinic and at home on waking in the morning at trough by the same methods included device, device validation, observer, number of measurements, conditions, posture and cuffs described previously (4). Namely, clinic BP (CBP) was measured once in each clinic visit. Home BP (HBP) was measured every day in the morning within 10 minutes after awakening in the sitting position.
  
  
• Insulin dose [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
  Patients were treated with insulin analogues using MDI, or twice-daily injections. The dose was estimated by medical records.
  
  
• Hypoglycemia [ Time Frame: Average time requires 5 yearsinsulin. ] [ Designated as safety issue: Yes ]
  Patients were treated with insulin analogues using MDI, or twice-daily injections. The dose was estimated by medical records.
  
  
• Hypoglycemia [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
  Hypoglycemia and the number of time per day were assessed by medical examination owing to interview.
  
  
• Microvascular complications including renal anemia [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
  They were assessment by the method mentioned above. As renal anemia, serum hemoglobin (Hb) was measured by cyanmet-hemoglobin method using commercial reagent.
  
  
• Macrovasular complications [ Time Frame: Average time requires 5 years ] [ Designated as safety issue: Yes ]
  They were confirmed by medical history, including contents of treatment. New or worsened (recurrent) events were defined based on clinical manifestations and treatment throughout the study.
  
  

Patients were treated with diet, exercise, and/or oral conventional pharmacotherapy combined with insulin. Oral conventional pharmacotherapy consisted of α-glycosidase inhibitors (α-GI), sulfonylurea (SU), biguanide (BG), thiazolidinedione (TZD), or combinations of these agents. Insulin therapy consisted of subcutaneous injections of long-acting insulin analogues prior to sleep and bolus subcutaneous injections of rapid-acting insulin analogues in multiple daily injections, or subcutaneous injections of mixed insulin analogues twice a day. In spite of the treatments, when the physician in charge judged that their values of HbA1c were inappropriate, the physician added the pharmacotherapy combined the insulin to incretin-based therapy. 2.3.2. For ethical reasons, patients were treated with various anti-hypertensive, anti-diabetic, anti-dyslipidemia and/or anti-hypercoagulation agents during the course of the study by the patients' own doctors as a part of continuing standard medical care. As to the drugs that have been used for the treatment of other disorders and its complication since the time before the study, the content should not be changed during the study in principle unless the complication is cured. If any new complication occurs during the study period, an appropriate treatment is given by the judgment of investigator.